Heritability estimates identify a substantial genetic contribution to risk and outcome of intracerebral hemorrhage
| Autor: | Natalia S. Rost, Scott Silliman, Jonathan Rosand, Valerie Valant, James F. Meschia, Steven M. Greenberg, Jaume Roquer, Joan Montaner, Chelsea S. Kidwell, Jeremiasz M. Jagiella, Andrzej Urbanik, Daniel Woo, Guido J. Falcone, Reinhold Schmidt, Israel Fernandez-Cadenas, Helena Schmidt, Joanna Pera, Christopher D. Anderson, Paul Freudenberger, Eva Maria Stögerer, Bradford B. Worrall, Sylvia Baedorf Kassis, Jordi Jimenez-Conde, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Alessandro Biffi, Bo Norrving, Pilar Delgado, Anand Viswanathan, Carolina Soriano, Agnieszka Slowik, Alison M. Ayres, William J. Devan, Magdy Selim, David L. Tirschwell, Joshua N. Goldstein, Devin L. Brown, Arne Lindgren, Björn M. Hansen, Kristin Schwab |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Genotype Genome-wide association study Disease Bioinformatics Severity of Illness Index Article Apolipoproteins E Risk Factors Genetic variation Severity of illness medicine Humans Genetic Predisposition to Disease Aged Cerebral Hemorrhage Advanced and Specialized Nursing Intracerebral hemorrhage Aged 80 and over Hematoma business.industry Case-control study Genetic Variation Heritability Middle Aged medicine.disease Prognosis Survival Rate Phenotype Case-Control Studies Female Neurology (clinical) Cardiology and Cardiovascular Medicine business Genome-Wide Association Study |
| Popis: | Background and Purpose— Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome. Methods— We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality. Results— ICH risk heritability was estimated at 29% (SE, 11%) for non- APOE loci and at 15% (SE, 10%) for APOE . Heritability for 90-day ICH mortality was 41% for non- APOE loci and 10% (SE, 9%) for APOE . Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non- APOE loci and at 12% (SE, 4%) for APOE . Conclusions— Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified. |
| Databáze: | OpenAIRE |
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